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卵泡液代谢组学根据子宫内膜异位症表型而不同。

The follicular fluid metabolome differs according to the endometriosis phenotype.

机构信息

Université de Paris, Faculté de Médecine, Paris, France; Assistance Publique-Hôpitaux de Paris (AP-HP), Hôpital Cochin (HUPC), Centre Hospitalier Paris Centre, Paris, France; Service d'Histologie-Embryologie-Biologie de la Reproduction, Paris, France; Département "Développement, Reproduction et Cancer", Institut Cochin, INSERM U1016, Université de Paris, Paris, France.

Université de Paris, Faculté de Médecine, Paris, France; Assistance Publique-Hôpitaux de Paris (AP-HP), Hôpital Cochin (HUPC), Centre Hospitalier Paris Centre, Paris, France; Département "Développement, Reproduction et Cancer", Institut Cochin, INSERM U1016, Université de Paris, Paris, France; Département de Gynécologie Obstétrique II et Médecine de la Reproduction, Paris, France.

出版信息

Reprod Biomed Online. 2020 Dec;41(6):1023-1037. doi: 10.1016/j.rbmo.2020.09.002. Epub 2020 Sep 4.

Abstract

RESEARCH QUESTION

Is there a follicular fluid-specific metabolic profile in deep infiltrating endometriosis (DIE) depending on the presence of an associated ovarian endometrioma (OMA) that could lead to the identification of biomarkers for diagnosis and prognosis of the disease?

DESIGN

In this prospective cohort study, proton nuclear magnetic resonance (H-NMR) experiments were carried out on 50 follicular fluid samples from patients presenting with DIE, associated or not associated with an OMA, and 29 follicular fluid samples from patients with infertility caused by a tubal obstruction.

RESULTS

Concentrations of glucose, citrate, creatine and amino acids such as tyrosine and alanine were lower in women with DIE than control participants, whereas concentrations of lactate, pyruvate, lipids and ketone bodies were higher. Metabolic analysis revealed enhanced concentrations of glycerol and ketone bodies in patients with OMA, indicative of an activation of lipolysis followed by beta-oxidation. Concentrations of lactate and pyruvate were increased in patients without OMA, whereas the concentration of glucose was decreased, highlighting activation of the anaerobic glycolysis pathway. Differences in concentrations of amino acids such as threonine and glutamine were also statistically relevant in discriminating between the presence or absence of OMA.

CONCLUSIONS

Results indicate a mitochondrial dysregulation in endometriosis phenotypes, with a modified balance between anaerobic glycolysis and beta-oxidation in OMA phenotypes that could affect the fertility of women with endometriosis. As the composition of the follicular fluid has been shown to be correlated with oocyte development and outcome of implantation after fertilization, these findings may help explain the high level of infertility in these patients.

摘要

研究问题

是否存在一种与卵巢子宫内膜异位囊肿(OMA)相关的、在深部浸润型子宫内膜异位症(DIE)患者的卵泡液中特异的代谢谱,这种代谢谱可以作为疾病诊断和预后的生物标志物?

设计

在这项前瞻性队列研究中,对 50 例伴有或不伴有 OMA 的 DIE 患者和 29 例因输卵管阻塞而导致不孕的患者的卵泡液进行了质子磁共振(H-NMR)实验。

结果

与对照组相比,DIE 患者的卵泡液中葡萄糖、柠檬酸、肌酸和酪氨酸、丙氨酸等氨基酸的浓度较低,而乳酸盐、丙酮酸、脂质和酮体的浓度较高。代谢分析显示,伴有 OMA 的患者中甘油和酮体的浓度升高,表明脂肪分解继而β氧化被激活。不伴有 OMA 的患者中乳酸盐和丙酮酸的浓度升高,而葡萄糖的浓度降低,这表明无氧糖酵解途径被激活。区分是否存在 OMA 时,苏氨酸和谷氨酰胺等氨基酸的浓度差异也具有统计学意义。

结论

结果表明,子宫内膜异位症表型中存在线粒体功能障碍,伴有 OMA 的表型中无氧糖酵解和β氧化之间的平衡发生改变,这可能影响子宫内膜异位症患者的生育能力。由于卵泡液的成分已被证明与卵母细胞发育和受精后胚胎着床的结果相关,这些发现可能有助于解释这些患者不孕率高的原因。

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